The National Institute of General Medical Sciences (NIGMS)
of the NIH invites applications for competing continuation of eligible
Centers of Biomedical Research Excellence (COBRE) grants. The objective of
the COBRE initiative is to strengthen an institution's biomedical research
infrastructure through the establishment of a thematic, multi-disciplinary
center and to enhance the ability of investigators to compete independently
for National Institutes of Health (NIH) individual research grants or other
external peer-reviewed support. COBRE awards are supported through the
Institutional Development Award (IDeA) Program, which aims to foster
health-related research by increasing the competitiveness of investigators at
institutions located in states with historically low aggregate success rates
for grant awards from the NIH.

(Now Expired June 8, 2013 per issuance of PAR-13-243), Originally September 26, 2014

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in
the PHS398
Application Guide except where instructed to do otherwise (in this FOA or
in a Notice from the NIH Guide
for Grants and Contracts). Conformance to all requirements (both in
the Application Guide and the FOA) is required and strictly enforced. While
some links are provided, applicants must read and follow all application
instructions in the Application Guide as well as any program-specific
instructions noted in Section IV. When
the program-specific instructions deviate from those in the Application Guide,
follow the program-specific instructions. Applications that do not
comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all
grant programs to electronic submission using the SF424 Research and Related
(R&R) format and is currently investigating solutions that will accommodate
NIH’s multi-project programs. NIH will announce plans to transition the
remaining programs in the NIH
Guide to Grants and Contractsand on NIH’s Applying Electronically website.

Program Description:
The goals of the Centers of Biomedical Research Excellence (COBRE) program are
(1) to strengthen an institution's biomedical research infrastructure through
the establishment of a thematic multi-disciplinary center and (2) to enhance
the ability of investigators to compete independently for NIH individual
research grants or other external peer-reviewed support. It is emphasized that
a significant part of the COBRE program is to build and develop thematic
multi-disciplinary research centers. COBRE support consists of three sequential
five-year phases. Phase I focuses on developing research infrastructure
and providing junior investigators with formal mentoring and research project
funding to help them acquire preliminary data and successfully compete for
independent research grant support. Phase II, which is the focus of this
FOA, is intended to strengthen the center through further improvements in
research infrastructure and to continue development and support of a critical
mass of investigators with shared scientific interests. It is therefore
expected that progress will have been made toward establishing centers that can
compete independently for external peer-reviewed center or program project
grant support. In some instances centers may be more effectively maintained by
the centers’ investigators competing for individual investigator-initiated
research support. Phase III provides support for maintaining COBRE research
cores developed during phases I and II.

Objectives: The purpose of this FOA is to allow institutions holding COBRE
Phase I grants to compete for continuation support to promote the development
of thematic, multi-disciplinary centers. Progress must be commensurate with
previous support and must substantiate the merit of continued NIH research
funding. It must be demonstrated that previous support has allowed the center
to achieve specific benchmarks, which include the acquisition of independent
status by the junior investigators and evidence that the competitiveness of
these investigators for other NIH, Federal or non-Federal external peer-reviewed
research grant support has been enhanced. Furthermore, evidence that a critical
mass of investigators has been (or is being) established must be shown. These
benchmarks are a measure of successful mentoring and scientific leadership by
the PD/PI and the established biomedical research faculty. Leadership is also
demonstrated by showing that the infrastructure necessary for the continued
functioning of the center (facility improvements, modernization/acquisition of
equipment, implementation of administrative resources, etc.) is in place, and
that the institution is committed to maintain the resources and infrastructure
that have been established through prior COBRE support.

Overall
Center Organization and Management plan: Applications must
describe an overall center organization and management plan that justifies
continued support of a thematic multi-disciplinary center for COBRE Phase II,
and a description of the unique research opportunities that have been and will
continue to be provided to the investigators and to the institution. The
efforts and ongoing research of all center investigators should be described in
the context of developing an independent and sustainable multi-disciplinary
program. The research plan must contain the descriptions of at least three and
no more than five individual research projects. An administrative core with a
detailed development and mentoring plan must be included. In addition, support
for research core facilities necessary to carry out the objectives of the
center may be proposed.

The leadership and direction of the COBRE are provided by
the Program Director/Principal Investigator (PD/PI). He/she has the primary
responsibility for administering the program and overseeing the development of
the center and its associated core facilities. The current PD/PI may continue
to serve in this role or a new PD/PI may be appointed. In either case, the
PD/PI must be an established biomedical or behavioral research scientist who
will ensure that high-quality research is performed, and who has the experience
and qualifications to effectively administer and integrate all program
components of the program. A minimum time commitment of 3 person months is
required for this individual. However, up to 6 person months will be supported
for mentoring and administrative oversight of the center.

No non-Federal matching funds are required for these
applications. However, evidence of institutional commitment must be included
and explicitly described and/or documented. The level of institutional commitment
will differ across applicant institutions because of the variability of
resources available at those institutions. At a minimum, a letter of support
from a senior institutional official (e.g., President or Dean) should outline
the commitment of resources and facilities to sustain and support the COBRE
throughout the funding period and plans to maintain these resources beyond the
period of grant support.

Applications must briefly describe the institutional
environment and resources available to investigators, and indicate how prior
COBRE support has improved facilities or made available new and collaborative
resources (e.g., laboratory facilities, patient populations, laboratory space
and personnel). If support for instrumentation to augment existing or establish
new core facilities is requested, the application should identify the needs of
each component research project for the core(s) and how this instrumentation
will facilitate the center’s research.

Administrative
Core: A clear plan for the transition to and attainment of
independent status for junior investigators and for the continued development
of early career investigators must be included. This plan should also describe
how the center as a whole intends to make the transition from support of
multi-disciplinary COBRE research projects to competitive grant support
obtained through applications submitted by its faculty members to relevant NIH
Institutes and Centers or other appropriate Federal or non-Federal agencies or
organizations. All project investigators, regardless of their career status,
must submit independent investigator-initiated RPG applications by the end of
two years of COBRE support to be eligible for continued COBRE funding.

The development plan must include both formative and
summative evaluation strategies detailing specific milestones, including, but
not limited to, the acquisition of independent status by the investigators;
competition for NIH, Federal or non-Federal external peer-reviewed research
grant support; and publications in peer-reviewed journals. Faculty development
should include a mentoring plan that involves oversight by established senior
faculty members assigned as mentors, constructive evaluations by members of the
External Advisory Committee (EAC), and coordinated management of all of these
individuals by the PD/PI of the COBRE program. Additional oversight may be
augmented through the use of an internal advisory committee, but this committee
should not act as a substitute for the EAC.

Each junior investigator must have at least one mentor. The
mentor must be an established investigator who has demonstrated the ability to
advise others on the acquisition of external support and the maintenance of an
independent research laboratory. In some instances a suitable mentor may not be
available within the applicant's institution and it is therefore acceptable to
enlist appropriate mentors from outside institutions. Mentors may be
compensated for up to 1.8 person months of effort and should be listed in the
Administrative Core's budget section of the application and not in the
individual research projects' budget sections. Investigators should clearly
designate in the text the identity of their mentors and describe their
qualifications, both scientific and advisory, that make them appropriate to
assist in the oversight of the project.

An investigator who has acquired independent status through
the award of an RPG may continue to participate as a COBRE research project
investigator by proposing a new project that does not overlap with his/her
other award(s). New COBRE projects must be reviewed by the PD/PI and the EAC.
The PD/PI must communicate the EAC recommendation to the NIGMS for their
programmatic and administrative review. An investigator who has acquired independent
RPG support may direct a COBRE core facility or serve as a mentor. In either
case, investigators should not be excluded from center activities and should be
encouraged to participate in collaborative research efforts. In some instances,
a project leader may be considered for removal from the COBRE program if a
review by the EAC indicates a failure by the investigator to make significant
progress toward achieving the specific aims of his/her project or, as noted
above, failure to submit an investigator-initiated RPG application by the end
of two years of COBRE support.

Each COBRE application must include an EAC comprised of 3-5
scientists with national scientific reputations in their fields. Their
expertise must be directly relevant to the scientific theme of the COBRE. The
EAC critiques the scientific progress of the COBRE and also offers advice on
scientific matters to the COBRE PD/PI. The EAC activities include developing
and planning concepts and programs, encouraging and assisting faculty development
and mentoring, identifying resources, evaluating the development of the center,
evaluating the progress of the individual research projects, and evaluating the
junior investigators' progress toward acquiring independent status. The PD/PI
will share the advice and critiques provided by the EAC with other COBRE
investigators at the center. The EAC also will review and recommend candidate
investigators for replacement/substitute projects, as required, before such
requests are forwarded to the NIGMS for programmatic review. The EAC must meet
at least twice per year. Video-, teleconferencing or other means may be used in
situations where it would be difficult to hold an in-person meeting. A summary
of the issues discussed at each EAC meeting, recommendations made, and actions
taken must be included in the yearly progress reports submitted to the NIGMS.

A pilot project program may be proposed. The description of
a pilot project must include a plan for the solicitation of applications, their
review and funding prioritization, oversight and evaluation procedures, and
assurance of full compliance with all applicable federal policies, rules, and
guidelines for research involving human subjects, vertebrate animals, and/or
biohazards. The pilot project(s) must be reviewed by EAC. The recommendation
from EAC must be submitted to NIGMS for programmatic review. Research plans for
individual pilot research projects should not be included in the application.

Research
Core Facilities: Funds may be requested to maintain or
establish core facilities. In addition to personnel and supply costs, the
acquisition of new equipment and modernization of instrumentation may be
proposed. Alteration and Renovation (A&R) of core facilities cannot be
proposed, nor can funds be used to support A&R. The applicant must
demonstrate that each core will serve the scientific needs of the individual
research projects and must show how each core will impact the development and
sustainability of the center. Although the COBRE award is not intended to
replace support for ongoing investigator-initiated research projects, all
center participants, including the mentors, as well as other non-center
investigators at the institution, may use these facilities. Additional
justification may be offered by showing how a core facility will benefit these
individuals and improve the research infrastructure of the institution. Each
core description should indicate the qualifications of personnel selected to
manage the facility and/or plans to recruit personnel to operate the core, if
needed, and the proposed business plan for operation of the core including
prioritization of the service requests, charge back fees for non-COBRE users.
Furthermore, the PD/PI should indicate any institutional commitment to support and
maintain the proposed facilities.

Individual
Research Projects: The COBRE center must contain at least
three and up to five individual research projects. The individual research
projects should stand alone but share a common thematic scientific focus. Each
research project should be supervised by a single investigator who is
responsible for ensuring that the specific aims of that project are met. Each
individual research project should describe the specific aims in the selected
area of research and the goals for the long term, and delineate the design
principles supporting the research or the hypotheses to be tested. Preliminary
studies are not required for COBRE applications, but applicants with
preliminary results should describe them. In the absence of preliminary
results, applicants should describe the rationale and scientific basis for the
proposed research. Each research project should describe its relationship to
the area of multi-disciplinary research that is the focus of the COBRE. It should
also critically assess the existing knowledge and approaches that have been, or
are being, directed in the area with a specific emphasis on how the
multi-disciplinary COBRE approach will advance the field. Moreover, the
importance and health relevance of the proposed research should be concisely
stated.

Mentoring and development of investigators who are not yet
established are a significant part of the creation and establishment of the
critical mass of successful investigators necessary to make up a research
center. The participation of junior investigators is integral to this concept
and is strongly encouraged. A junior investigator is defined as an individual
who does not have, or has not previously had external, peer-reviewed Research
Project Grant (RPG) or Program Project Grant (PPG) support from either Federal
or non-Federal sources for which the individual is named as the PD/PI. A junior
investigator who is supported by IDeA Networks of Biomedical Research
Excellence (INBRE) is not eligible to receive research support from COBRE.
This FOA also includes continued mentoring of and support for qualified early
career investigators to promote the success and integrity of the research
center. Furthermore, this FOA encourages the recruitment and/or support of
qualified, more senior investigators to facilitate the growth and independence
of the center. Qualified investigators must demonstrate a record of
productivity. Taken together, these efforts are intended to promote the
development of an independent and successful research center. To this end, any
qualified investigator is eligible to participate as a project investigator in
the center.

Junior investigators must make an initial minimum commitment
of 6 person months annually. Established investigators must make an initial
commitment of at least 3 person months annually. It is recognized that during
the development of an investigator's career (for example, the acquisition of
other research support) it may be necessary to reduce these levels of
commitment. PD/PIs should consult with NIGMS program staff regarding
appropriate reductions. Each project investigator should indicate in the
Biographical Sketch his/her current and previous history of peer-reviewed
research support.

Investigators must hold a faculty appointment (or equivalent
at research institutes) at the time the award is made. Moreover, the applicant
institution must demonstrate, in a letter(s) from the appropriate senior
institutional official(s), a clear commitment to support this faculty appointment
independent of the outcome of the COBRE grant application. Individuals holding
postdoctoral fellowships or other positions that lack independent faculty
status are not eligible to lead COBRE research projects. The PD/PI of the COBRE
is not eligible for research project support nor can he/she use COBRE funds to
supplement research activities within his/her laboratory.

COBRE support cannot be provided for a project that overlaps
with or is significantly similar to an investigator-initiated research program
that is already funded from another source. Furthermore, if a COBRE supported
investigator obtains additional external support, COBRE support of the project
must be discontinued if it is significantly similar to, or overlaps with, the
newly funded project. Conversely, COBRE support can be continued if there are
sufficient differences between the COBRE and non-COBRE supported projects,
since the investigator is obligated to complete his/her COBRE project.

Section II. Award Information

Funding Instrument

Grant

Application Types Allowed

Renewal
Resubmission

The OER
Glossary and the PHS398 Application Guide provide details on these application
types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH
appropriations, and the submission of a sufficient number of meritorious
applications.

Award Budget

The annual budgets must not exceed $1.5 million in direct
costs. .

Award Project Period

Five years.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applications will only be accepted from institutions that
are in IDeA states and currently hold a Phase I COBRE award.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in theNIH
Grants Policy Statement, are not allowed.

Required Registrations

Applicant organizations must complete the following registrations
as described in the PHS398 Application Guide to be eligible to apply for or
receive an award. Applicants must have a valid Dun and Bradstreet Universal
Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due
date. Applicant organizations are strongly encouraged to start the registration
process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal
Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always encouraged
to apply for NIH support.

Multiple PD(s)/PI(s) are not allowed for this FOA.

The NIH recognizes a compelling need to promote diversity in
the biomedical, behavioral, clinical and social sciences workforce. The NIH
expects efforts to diversify the workforce to lead to the recruitment of the
most talented researchers from all groups; to improve the quality of the
educational and training environment; to balance and broaden the perspective in
setting research priorities; to improve the ability to recruit subjects from
diverse backgrounds into clinical research protocols; and to improve the
Nation’s capacity to address and eliminate health disparities.

Accordingly, the NIH continues to encourage institutions to
diversify their trainee and faculty populations and thus to increase the
participation of individuals currently underrepresented in the biomedical,
clinical, behavioral, and social sciences such as: individuals from
underrepresented racial and ethnic groups, individuals with disabilities, and
individuals from socially, culturally, economically, or educationally
disadvantaged backgrounds that have inhibited their ability to pursue a career
in health-related research. Institutions are encouraged to identify candidates
who will increase diversity on a national or institutional basis. The NIH is
particularly interested in encouraging the recruitment and retention of the
following classes of candidates:

A. Individuals from racial and ethnic groups that have been
shown by the National Science Foundation to be underrepresented in
health-related sciences on a national basis (see http://www.nsf.gov/statistics/ .
Nationally, groups found to be underrepresented in biomedical and behavioral
research include, but are not limited to, African Americans, Hispanic
Americans, Native Americans (including Alaska Natives), and natives of the U.S.
Pacific Islands. In addition, it is recognized that underrepresentation can
vary from setting to setting and individuals from racial or ethnic groups that
can be convincingly demonstrated to be underrepresented by the grantee
institution should be encouraged to participate in this program.

B. Individuals with disabilities, who are defined as those
with a physical or mental impairment that substantially limits one or more
major life activities.

C. Individuals from disadvantaged backgrounds who are
defined as:

Individuals who come from a family with an annual income below
established low-income thresholds. These thresholds are based on family size,
published by the U.S. Bureau of the Census; adjusted annually for changes in
the Consumer Price Index; and adjusted by the Secretary for use in all health
professions programs. The Secretary periodically publishes these income levels
at http://aspe.hhs.gov/poverty/indix.shtml. For individuals from low income
backgrounds, the institution must be able to demonstrate that such candidates
have qualified for Federal disadvantaged assistance or they have received any
of the following student loans: Health Professional Student Loans (HPSL), Loans
for Disadvantaged Student Program, or they have received scholarships from the
U.S. Department of Health and Human Services under the Scholarship for
Individuals with Exceptional Financial Need.

Individuals who come from a social,
cultural, or educational environment such as that found in certain rural or
inner-city environments that have demonstrably and recently directly inhibited
the individual from obtaining the knowledge, skills, and abilities necessary to
develop and participate in a research career. Recruitment and retention plans
related to a disadvantaged background are most applicable to high school and
perhaps undergraduate candidates, but would be more difficult to justify for
individuals beyond that level of achievement.

Applications will be accepted from institutions that are in
IDeA states and currently hold a Phase I COBRE award.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission
Applications from the PHS398 Application Guide.

Section IV. Application and Submission Information

1. Address to Request
Application Package

Applicants are required to prepare applications according to
the current PHS 398 application forms in accordance with the PHS 398 Application
Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the PHS398
Application Guide, except where instructed in this funding opportunity
announcement to do otherwise. Conformance to the requirements in the
Application Guide is required and strictly enforced. Applications that are out
of compliance with these instructions may be delayed or not accepted for review.

Application Submission

Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application,
including the checklist, and three signed photocopies in one package to:

All page limitations described in the PHS398 Application
Guide and the Table of
Page Limits must be followed, with the following requirements:

The application should be organized and assembled in the
order as follows:

Face
Page

Use Form 1 of the PHS 398. On Line 1, include the title
that best represents the nature of the COBRE Program. On Line 2, provide the FOA
number PAR-12-224 and the FOA title “Limited Competition: Renewal of Centers
of Biomedical Research Excellence”. Information for the PD/PI should be
entered on the PHS398 face page. Please remember that the PD/PI must be
registered in the eRA Commons prior to application submission. The budget
figures should be taken from the consolidated program budget (see below).

Description
Page

Use Form 2 of the PHS 398. An abstract describing proposed
COBRE center is required and should be placed in the Project Summary area. The
length of abstract must not exceed the space provided.

Key Personnel including the PD/PI, core directors, research
project leaders, and other key professional and administrative members of this
Program should be placed in the area of Performance Sites and Key Personnel. Do
not separate key personnel into each project section.

Table
of Contents

Applicant must customize the PHS 398 Table of Contents to
specifically identify the section of the application. All sections including
the content each core and research project must be separately identified in the
customized table of contents.

Detailed
Budget Pages for Initial Budget Period and Entire Proposed Period of Support

Use Form 4 and 5 of the PHS 398. A summary or composite
budget page should be provided for the Center which should preceed all other
individual and entire proposed project period budget pages. A detailed budget
for the initial budget period (form page 4) and the budget for the entire
proposed project period (form page 5) must be provided for each core and
individual research project. Each budget page should be clearly labeled with the
name of the core or research project. A detailed justification for each item
requested, including supply costs and other expenses, must be provided. The
justification should be placed immediately after each budget section. Do not
separate the individual budgets into each core or research project section.

An applicant may request a budget for direct costs no more
than $1.5 million per year, excluding facilities and administrative (F&A)
costs on consortium arrangements. If items are requested as direct costs that
are normally treated as F&A costs (for example, computers and general
office supplies), the applicant must provide a strong justification for those
items and demonstrate that the cost is commensurate with the benefit that
particular item of cost will have on the associated project .

The PD/PI of the COBRE is not eligible for research project
support, nor can he/she use COBRE funds to supplement research activities
within his/her laboratory.

Core facilities and individual research projects that are
proposed to begin in the first year should have a detailed budget for the
initial budget period (form page 4) and a corresponding budget for the entire
proposed project period (form page 5). Although the applicant can propose
research projects and/or support for core facilities to begin in later years,
each year's budget should include costs for only those projects or cores that
will be active in that year.

Funds may be used to recruit additional faculty who
complement the scope of the proposed program. Recruitment funds are limited to
$200,000 per year for each position and may be used to recruit either junior or
established senior investigators. These funds may be used for salary, supplies,
and/or equipment costs.

PD(s)/PI(s) of the Centers funded through this FOA should
budget for and will be expected to attend an annual two-day meeting in
Bethesda, Maryland with NIGMS staff.

Funds for alteration & renovation of laboratory
facilities should not be proposed and will not be supported.

When a grant application includes research activities that
involve institutions other than the grantee institution, it is considered a
consortium effort. Such activities may be included in the COBRE grant
application, but it is imperative that a consortium application be prepared so
that the programmatic, fiscal, and administrative considerations are explained
fully. In addition, the thematic scientific focus of the COBRE must be evident
in applications that include consortia arrangements. Applicants for COBRE
grants should exercise great diligence in preserving the interactions of the
participants and the integration of the consortium project(s) with those of the
parent institution because synergism and cohesiveness can be diminished when
projects are located outside of the parent institution.

Funds cannot be used at collaborative institutions in
non-IDeA states. However, funds may be used in other IDeA and non-IDeA states
for fee-for-service activities that include activities such as learning new
techniques, sample and data analysis, workshops etc.

Biographical
Sketches

All Biographical Sketches should be grouped together with
the PD/PI's biographical sketch presented first followed by all other sketches
in alphabetical order. Do not separate the biographical sketches into each
project section.

Resources

Resources including existing equipment, instrumentation and
laboratory space for cores and research projects should be described using the
PHS398 Resources form page and instructions. Although there is no page limit
for resource section, it should be concise and contain only information that is
not included in the Research Strategy section for that corresponding core or
research project. Do not include information required by the FOA, such as
methods, that belongs in the page-limited Research Strategy sections. Resources
section may be divided into resources available for each core/and or project
but all sections should appear together. Do not include Resources form in
individual projects and cores.

If you do not want the applicants to deviate from the
Application Guide for any of the Components listed above, then you must DELETE
ALL headings listed above. Otherwise, keep ONLY the headings in which you are adding
information about the content and form of the above listed sections, and
describe each section separately, with its own heading. Include ONLY
instructional information that is different from the application guide. Do NOT
include any sections that are part of the Research Plan Component (which should
be placed below).

Research Plan

All instructions in the PHS398 Application Guide must be
followed, with the following additional instructions:

The Research Plan for each section consists of the following
components, as applicable. All page limits include all tables and figures. Do
not use components without page limits (1, 2, and 6 to 15) to circumvent the
page limits of the Research Strategy.

1. Cover page

2. Description page

3. Introduction (1 page, Resubmission Applications
only)

4. Specific Aims (1 page)

5. Research Strategy (12 pages)

6. Bibliography and References Cited

7. Protection of Human Subjects

8. Inclusion of Women and Minorities

9. Targeted/Planned Enrollment Table

10. Inclusion of Children

11. Vertebrate Animals

12. Consortium/Contractual Arrangements

13. Letters of Support

14. Resource Sharing Plan

15. Check List

Specific
Requirements for Individual Sections:

Cover page (Do
NOT use PHS 398 face page)

For each individual core and research project, a cover page
should be included that indicates the project title, the name of the
investigator supervising the project, the name of the mentor(s) if applicable,
whether human subject/human subject materials will be used in the project, and
whether vertebrate animals will be used in the project.

Description page (PHS 398 Form 2)

An Abstract of the proposed core or project is required.
The length of the abstract must not exceed the space provided. Do not include a
key personnel list in individual core or project section.

Introduction (Resubmission Application only, 1 page for
each section)

The Introduction must include responses to the criticisms
and issues raised in the prior Summary Statement, which summarizes the
substantial additions, deletions, and changes. Insert the Introduction before
the Research Strategy of each section, identifying within the Research Strategy
the changes made by clearly bracketing, indenting, or changing typography,
unless the changes are so extensive as to include most of the text. This
exception should be explained in the Introduction. Do not underline or shade
changes.

Progress and Accomplishments (6 pages)

A description of the major progress and accomplishments made
in COBRE Phase I in the following areas:

Research productivity as measured by scientific publications in
the peer reviewed journals and presentations at scientific meetings and other
conferences.

Research grants submitted to and awarded by NIH or other funding
agencies.

Improvement of research infrastructure as measured by utilization
of core facilities by COBRE and non-COBRE investigators, and increased research
productivity associated with core support.

Increased critical mass of investigators as evidenced by
successful recruitment of science faculty through COBRE support.

Other metrics as defined by the applicant that demonstrate
accomplishments during COBRE phase I.

Publications produced in COBRE Phase I should be listed in "Bibliography
and References Cited/Progress Report Publication List" section.

Overall Center Organization and Management Plan

Specific Aims (1 page)

Research Strategy (12 pages)

Justification
of a continued second five-year support for a thematic multidisciplinary COBRE
program.

A
research strategy that describes the organization and component functions of
the COBRE. The plan should demonstrate the applicant's knowledge, ingenuity,
practicality, and commitment to developing and maintaining a significant and
productive research program.

A
description of the existing equipment and instrumentation for conducting
studies aimed at developing a nationally competitive biomedical research
program. Sharing research resources among IDeA programs is strongly
encouraged. Applicants should describe plans for utilizing equipment and
instrumentation supported by existing COBRE or IDeA Networks of Biomedical
Research Excellence (INBRE) awards.

A
description of and justification for the proposed individual research projects
and core service facilities that collectively will contribute to the center.

A
description of how the efforts of each research project leader will contribute
to the establishment of a multi-disciplinary research center.

Administrative Core

Specific Aims (1 page)

Research Strategy (12 pages)

A clear
and full explanation of the necessary administrative, fiscal, and scientific
aspects of the proposed COBRE.

A
description of the research and research training or career development goals
and capabilities of the proposed COBRE.

A
mentoring plan addressing the development of junior investigators for their
transition to and attainment of independent investigator status.

A
formative and summative evaluation strategy with specific milestones.

Description
of pilot project program (optional)

Research Cores

Specific Aims (1 page for each core)

Research Strategy (12 pages for each core)

The
impact of proposed cores on the development of the center and how they will
serve the scientific needs of the individual research projects.

The
qualifications of personnel selected to manage the facilities.

A
description of how the cores will be operated.

Institutional
commitment, if any, to support and maintain the proposed cores.

Research Projects

Specific Aims (1 page for each project)

Research Strategy (12 pages for each project)

The
experimental design principles supporting the research or the hypothesis to be
tested should be clearly delineated.

Preliminary
data is not required, but should be included if the data is available.

Applicants
should describe the nature and scope of any scientific research collaborations
within or cross institution.

Letters indicating institutional commitment and any letter
of support for the proposed center and research core (if applicable) should be
placed immediately after the Research Strategy of the overall center
organization and management plan and corresponding core, respectively. As
necessary, each project section can be concluded with letters of commitment
from mentors and, as needed, letters of commitment from collaborators and/or
consultants.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398
Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH. Applications that are
incomplete will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact - Overall

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the COBRE center to exert a sustained, powerful influence on the research field(s) involved, in consideration
of the following review criteria and additional review criteria (as applicable
for the COBRE center proposed). The overall impact/priority score will also
take into consideration the extent to which the individual cores and projects
enhance the strength of the overall center and the importance of the individual
cores and projects to the success of the center.

Scored Review Criteria - Overall Center Application

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the program address an important problem or a
critical barrier to progress in the field? If the aims of the program are achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Progress
and Accomplishments

Has previous support allowed the center to achieve
specific benchmarks, which include the acquisition of independent status by the
junior investigators, publishing data in peer-reviewed journals, and evidence
that the competitiveness of these investigators for other NIH, Federal or
non-Federal external peer-reviewed research grant support has been enhanced?

Is there evidence that a critical mass of
investigators has been (or is being) established?

Have new investigators been recruited to the center
and have these efforts been successful in increasing the biomedical or
behavioral research capacity of the institution?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Does the PD/PI demonstrate leadership by showing that
the infrastructure necessary for the continued functioning of the center (e.g.,
facility improvements, modernization/acquisition of equipment, implementation
of administrative resources, etc.) is in place, and that the institution is
committed to maintaining the resources and infrastructure that have been
established through prior COBRE support?

Has the PD/PI shown the ability to lead, develop, and
direct the COBRE to establish thematic collaborative research efforts? Has the PD/PI
shown effective leadership and judgment in the selection of research projects
in terms of research projects being of high quality and significance? Has the PD/PI
shown effective leadership in directing and managing the mentoring plan
required to move the investigators toward independent status? Does the PD/PI
present a plan for the continued development of investigators to independent
status?

If a new PD/PI has been selected, has the new PD/PI
provided evidence of successfully mentoring graduate students, postdoctoral
fellows and junior investigators as well as leading a large research group?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented?
If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Center
Organization and Management Plan

Will the proposed organization and management plan
provide appropriate support for a thematic, multi-disciplinary center durning
the next five-year period? Does the overall plan justify continued support of a
thematic multi-disciplinary center for an additional five years?

Are the efforts and ongoing research of all center
investigators described in the context of developing an independent and
sustainable multi-disciplinary program? Are the proposed projects related to
and consistent with the overall goals of center?

If the PD/PI plans to recruit new investigators in
the future, are these plans consistent with the thematic focus of the center?
Are the senior investigators’ research projects related to, and do they advance,
the thematic focus of the COBRE?

If support for instrumentation to augment existing or
establish new core facilities is requested, does the application identify the
needs of each component research project for the core(s) and how this
instrumentation will facilitate the center’s research?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Does the application describe the institutional
environment and resources available to investigators, and indicate how prior
COBRE support has improved facilities or made available new and collaborative
resources (e.g., laboratory facilities, patient populations, laboratory space
and personnel)?

Review Criteria for Cores

Reviewers will score each core based on the criteria
provided.

Administrative
Core

Does the administrative core include a clear plan for
the transition to and attainment of independent status for junior investigators
and for the continued development of early career investigators and describe
how the center as a whole intends to make the transition from support of
multi-disciplinary COBRE research projects to competitive grant support?

Does the development plan include a mentoring plan
that involves oversight by established senior faculty members assigned as
mentors, constructive evaluations by members of the External Advisory
Committee? Is there coordinated management of all of these individuals by the PD/PI
of the COBRE program?

Milestones and Evaluation: Has the PD/PI selected
appropriate and suitable evaluation strategies? Does the development plan
include both formative and summative evaluation strategies detailing specific
milestones for the acquisition of independent status by the investigators? Are
specific milestones identified and supported to measure progress toward
attaining long-range goals?

Has the PD/PI described the strategies and milestones
that will be applied in the future, describing what has worked and what needs
to be improved in terms of milestones?

Is the External Advisory Committee properly
constituted with the scientific expertise to critique the scientific progress
of the COBRE and offer advice on scientific matters to the COBRE PD/PI?

If a pilot project program is proposed, is there an
adequate plan to solicit applications, prioritize the projects and review their
methodology and research performance? Are plans adequate to assure compliance
with applicable federal policies and guidelines for research and research
protections?

Research
Core Facilities

Has the PD/PI provided the necessary oversight to
establish and maintain the necessary core resources and laboratory facilities
to carry out the objectives of the application?

Do the core resources and facilities serve the
scientific needs of the individual research projects?

Are the personnel who direct the core facility as
well as the technical staff who operate the core facility well qualified?

Has the PD/PI obtained institutional commitments
sufficient to ensure that the resources and facilities required to sustain the
center are present?

For requests of new core facilities: is the request
justified in terms of the need for the core as it is related to the COBRE
thematic research focus?

Review Criteria for Individual
Research Projects

For each research project, reviewers will consider
each of the review criteria below in the determination of scientific and
technical merit and provide an overall impact/priority score, but will not give
separate scores for the individual criteria.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New Investigators,
or in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? Do the
investigators have complementary and integrated expertise; are their leadership
approach, governance and organizational structure appropriate for the project?

Are the strengths, academic qualifications and
biomedical expertise of the project investigator appropriate and sufficient for
research productivity? Does the project investigator have the potential and
ability to achieve independent status? Does the investigator demonstrate the
ability to compete successfully for investigator-initiated support? Does the
investigator publish his/her work in a timely manner? For project investigators
new to the COBRE, do they show career development potential and/or an ability
to achieve independent status?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the
plans for 1) protection of human subjects from research risks, and 2) inclusion
of minorities and members of both sexes/genders, as well as the inclusion of
children, justified in terms of the scientific goals and research strategy
proposed?

If this project involves community engagement and outreach
research, are there clear and detailed plans for identifying a health issue
that fits community priorities and academic capacity to respond? Are there
plans for developing a coalition of community and academic stakeholders and for
implementing evaluation strategies for the proposed projects? Is the research
characterized by substantial community input in the development of the proposed
study? Are community members, persons affected by the health condition,
disability or issue under study, or other key stakeholders in the community’s
health, full participants in each phase of the research, including conception,
design, conduct, analysis, interpretation, drawing of conclusions and
communication of results?

Can this project stand alone?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria - Overall

As applicable for the cores and projects proposed, reviewers
will evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of
minorities and members of both genders, as well as the inclusion of children. For
additional information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations - Overall

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign
Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by NIGMS, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall
impact/priority score.

Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and will
compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the NIGMS Advisory Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to
program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006
(Transparency Act), includes a requirement for awardees of Federal grants to
report information about first-tier subawards and executive compensation under
Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.